Medicines 6

Question 1

What is the starting dose for metformin?

Answer 1

For standard-release metformin tablets:
500 mg with breakfast for at least 1 week, then 500 mg with breakfast and evening meal for at least 1 week, then 500 mg with breakfast, lunch, and evening meal thereafter; maximum dose 2 g daily (in divided doses).

For modified-release metformin tablets:
Initially 500 mg once daily, then increased if necessary up to 2 g once daily, dose increased gradually, every 10–15 days, dose to be taken with evening meal.
Alternatively, dose increased to 1 g twice daily, dose to be taken with meals, alternative dose only to be used if control not achieved with once daily dose regimen. If control is still not achieved, then change to standard-release tablets.

Question 2

What are the symptoms that an adult patient would likely present with, to enable the diagnosis of sepsis (3 marks)? When recording a patients’ observations on a NEWS chart, what score should make you ‘think sepsis’?

Answer 2

(b) Likely symptoms (3 marks)
· Slurred speech (1/2 mark)
· Extreme shivering or muscle pain (1/2 mark)
· Passing no urine in a day (1/2 mark)
· Severe breathlessness (1/2 mark)
· Skin mottled or discoloured (1/2 mark)
· Patient feeling like they are going to die (1/2 mark)
NEWS score of ≥3 – think sepsis (1 mark)

Question 3

Outline the current treatment protocol for sepsis (4 marks)

Answer 3

· Current treatment relies on the Sepsis 6 pathway (1 mark)
· Administer high flow oxygen if needed (1 mark)
· Give broad spectrum antibiotics (1 mark)
· Give iv fluids (1 mark)
· Provide vasopressors and /or other organ support as required (1 mark)

Question 4

What medications are found in anticipatory medicines boxes and why?

Answer 4

• Cyclizine/metoclopramide (antiemetic) - nausea and vomiting

Cyclizine and metoclopramide not given together it cancels each other out

• Midazolam (Benzodiazepine)/ haloperidol (antipsychotic), usually given to treat agitation

levomepromazine (antipsychotic) - Severe agitation, nausea and vomiting

• Hysocine hydrobromide/Glycopyrronium (Antimuscarinics) - usually for chest secretions

morphine/diamorphine for pain

Question 5

What are Severe sepsis and septic shock defined as?

Answer 5

Severe Sepsis: sepsis with the dysfunction of one or more organ systems
Renal failure for example

Septic Shock: is the final stage where hypotension persists despite adequate fluid resuscitation

Question 6

Describe how sepsis alters (i) absorption, (ii) distribution, (iii) metabolism, and (iv) excretion and, for each of (i) to (iv), the advice you would give to the company with regard to the rational design of a new antibiotic taking the altered pharmacokinetics into consideration

Answer 6

• Absorption – decreased gastric and s/c absorption (GI system is non-essential and therefore often the first organ system to be shut down by the body, disseminated intravascular coagulation means reduce blood flow/supply to smaller vessels / peripheral system). (1 mark)
• This coupled with the desire for a rapid onset of action means company will need to formulate drug for administration via IV route. (1 mark)
• Distribution – Volume of distribution is higher in sepsis patients as a consequence of fluid resuscitation. (1 mark) (This can be problematic if antibiotic is particularly hydrophilic (e.g. beta-lactams / aminoglycosides). Lipophilic antibiotics such as fluoroquinolones / macrolides are less affected.)
• Company therefore need to consider relative hydrophilicity / lipophilicity of molecules they are synthesising. (1 mark)
• Metabolism – hepatic metabolism often altered / impaired, with phase 1 (CYP mediated) mechanisms being greatly affected by failure of the hepatic system. (1 mark)
• Need to consider likely route of metabolism for new drug. (1 mark)
• Excretion – significant changes often seen in renal function / urine output in sepsis patients. (1 mark) Want to rapidly achieve a therapeutic concentration without causing toxicity so will need to consider loading vs. maintenance dose. Dosing regime will depend on clearance rates (1 marks)

Question 7

HOW TO SPOT SEPSIS IN CHILDREN

Answer 7

Is breathing very fast
Has a ‘fit’ or convulsion
Looks mottled, bluish, or pale
Has a rash that does not fade when you press it
Is very lethargic or difficult to wake
Feels abnormally cold to touch

A child under 5 may have sepsis if he or she:

Is not feeding
Is vomiting repeatedly
Has not passed urine for 12 hours

Question 8

What are the important Renal levels to know with metformin use?

Answer 8

Before starting treatment with metformin, check renal function.
Do not start metformin treatment if estimated glomerular filtration rate (eGFR) is less than 30 mL/min/1.73 m2.

Stop treatment with metformin:
If eGFR is less than 30 mL/min/1.73 m2.

Review the dose of metformin if eGFR is less than 45 mL/min/1.73 m2

Question 9

Which antidiabetic medication is contraindicated in history of heart failure?

Answer 9

Pioglitazone

Contra-indications
Contra-indicationsFor pioglitazone
Diabetic ketoacidosis; history of heart failure; previous or active bladder cancer; uninvestigated macroscopic haematuria

MHRA/CHM advice: Pioglitazone cardiovascular safety (December 2007 and January 2011)
Incidence of heart failure is increased when pioglitazone is combined with insulin especially in patients with predisposing factors e.g. previous myocardial infarction. Patients who take pioglitazone should be closely monitored for signs of heart failure; treatment should be discontinued if any deterioration in cardiac status occurs.

Pioglitazone should not be used in patients with heart failure or a history of heart failure.

Question 10

If metformin is not effective as a monotherapy what would be the next steps?

Answer 10

If monotherapy is ineffective, consider adding one of the following:
A DPP-4 inhibitor (gliptins). - Metformin plus a DPP-4 inhibitor was moderately effective in controlling blood glucose levels and was associated with fewer hypoglycaemic events and may be beneficial in weight loss.

Pioglitazone. Metformin plus pioglitazone was most effective at reducing HbA1c levels at 24 months and preventing nausea but was associated with weight gain.

A sulfonylurea.

An SGLT-2 inhibitor — this may be considered in people taking metformin if a sulfonylurea is contraindicated or not tolerated, or the person is at significant risk of hypoglycaemia or its consequences.

Question 11

If a GLP-1 receptor agonist is added for people on insulin based treatment what medications should be changed or stopped?

Answer 11

Note: if a GLP-1 receptor agonist is added to insulin or an insulin secretagogue (sulfonylurea or meglitinide), consider reducing the dose of the latter agents to reduce the risk of hypoglycaemia. If a DPP-4 inhibitor is being taken, it should be discontinued on starting a GLP-1 receptor agonist, as the combination does not provide additional blood glucose control.

Question 12

What is the normal dose of carbimazole for hyperthyroidism?

Answer 12

Hyperthyroidism
for carbimazole
By mouth
Adult
15–40 mg daily continue until the patient becomes euthyroid, usually after 4 to 8 weeks, higher doses should be prescribed under specialist supervision only, then reduced to 5–15 mg daily, reduce dose gradually, therapy usually given for 12 to 18 months.
Hyperthyroidism (blocking-replacement regimen) in combination with levothyroxine
for carbimazole
By mouth
Adult
40–60 mg daily, therapy usually given for 18 months.

Question 13

What is Propylthiouracil indicated for and what advice is given to the patient regarding it?

Answer 13

Hyperthyroidism
for propylthiouracil
By mouth
Adult
Initially 200–400 mg daily in divided doses until the patient becomes euthyroid, then reduced to 50–150 mg daily in divided doses, initial dose should be gradually reduced to the maintenance dose.

Patients should be told how to recognise signs of liver disorder and advised to seek prompt medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, jaundice, dark urine, or pruritus develop.

Question 14

What is cabocystiene used for and when is it cautioned/contraindicated?

Answer 14

Reduction of sputum viscosity

Contra-indications
Contra-indications For carbocisteine
Active peptic ulceration

Cautions
Cautions For carbocisteine
History of peptic ulceration (may disrupt the gastric mucosal barrier)

Question 15

Why should alendronic acid be be swallowed whole, not crushed, chewed, or dissolved

Answer 15

If chewed or crushed it will have more contact with the eosopgheal tract leading to side effects

Question 16

What are the main things for patients to consider for counselling with patients on alendronic acid

Answer 16

Atypical femoral fractures

Patients should be advised to report any thigh, hip, or groin pain during treatment with a bisphosphonate.

Osteonecrosis of the jaw

During bisphosphonate treatment patients should maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms.

Osteonecrosis of the external auditory canal

Patients should be advised to report any ear pain, discharge from ear or an ear infection during treatment with a bisphosphonate.

Stop treatment if you experience any oesophageal symptoms such as dysphagia
Tablets should be swallowed whole and oral solution should be swallowed as a single 100 mL dose. Doses should be taken with plenty of water while sitting or standing, on an empty stomach at least 30 minutes before breakfast (or another oral medicine); patients should stand or sit upright for at least 30 minutes after administration.
Can take a 70mg weekly dose or a 10mg daily dose
Keep good oral hygiene

Question 17

What atrial fibrillation medication can cause

Answer 17

Amiodorone - it contains iodine which can cause hypo or hyperthyroidism

Thyroid function tests should be performed before treatment, then at 6-monthly intervals, and for several months after stopping treatment (particularly in the elderly). Thyroid stimulating hormone levels should be measured if thyroid dysfunction is suspected. Consult specialist if thyroid function is abnormal.

Question 18

What is important safety information regarding carbimazole?

Answer 18

Neutropenia and agranulocytosis
Manufacturer advises of the importance of recognising bone marrow suppression induced by carbimazole and the need to stop treatment promptly.

Patient should be asked to report symptoms and signs suggestive of infection, especially sore throat.
A white blood cell count should be performed if there is any clinical evidence of infection.
Carbimazole should be stopped promptly if there is clinical or laboratory evidence of neutropenia.
MHRA/CHM advice: Carbimazole: increased risk of congenital malformations; strengthened advice on contraception (February 2019)
Carbimazole is associated with an increased risk of congenital malformations when used during pregnancy, especially in the first trimester and at high doses (daily dose of 15 mg or more).

Women of childbearing potential should use effective contraception during treatment with carbimazole. It should only be considered in pregnancy after a thorough benefit-risk assessment, and at the lowest effective dose without additional administration of thyroid hormones—close maternal, fetal, and neonatal monitoring is recommended.

MHRA/CHM advice: Carbimazole: risk of acute pancreatitis (February 2019)
Cases of acute pancreatitis have been reported during treatment with carbimazole. It should be stopped immediately and permanently if acute pancreatitis occurs.

Carbimazole should not be used in patients with a history of acute pancreatitis associated with previous treatment—re-exposure may result in life-threatening acute pancreatitis with a decreased time to onset.

Question 19

Why is it important to counsel patients on finsateride to use contraception (condom)

Answer 19

Finasteride is excreted in semen and use of a condom is recommended if sexual partner is pregnant or likely to become pregnant.

MHRA/CHM advice: Finasteride: reminder of the risk of psychiatric side effects and of sexual side effects (which may persist after discontinuation of treatment) (April 2024)
Following a safety review of the available evidence, a patient alert card highlighting the risk of psychiatric and sexual side-effects associated with finasteride is being introduced to increase awareness. Healthcare professionals are reminded that finasteride has been associated with depression, suicidal thoughts, and sexual dysfunction (including decreased libido and erectile dysfunction, with some cases reported to persist after treatment discontinuation). Healthcare professionals are advised to ask patients if they have a history of depression or suicidal ideation before prescribing finasteride, and to monitor for these side-effects after starting treatment.

Question 20

What handling and storage advise should be given for finasteride?

Answer 20

Women of childbearing potential should avoid handling crushed or broken tablets of finasteride.

Question 21

Where should you apply HRT patches to?

Answer 21

Apply one patch on a clean, dry, unbroken area of the skin on the trunk below waistline twice a week

Question 22

What lifestyle changes can some one with osteoporosis implement?

Answer 22

Patients should be encouraged to increase their level of physical activity, stop smoking, maintain a normal BMI level (between 20–25 kg/m²), and reduce their alcohol intake to improve their bone health and reduce the risk of fragility fractures. For guidance on stopping smoking, see Smoking cessation.

Patients at risk of osteoporosis should also ensure an adequate intake of calcium and vitamin D. Calcium should preferably be obtained through increasing dietary intake; supplements may be used if necessary. A daily dietary supplement of vitamin D may be considered for those at increased risk of deficiency.

Question 23

what are the risks associated with estriol use?

Answer 23

Risk of endometrial cancer
The increased risk of endometrial cancer depends on the dose and duration of oestrogen-only HRT.

In women with a uterus using systemic preparations, the addition of a progestogen cyclically (for at least 10 days per 28-day cycle) reduces the additional risk of endometrial cancer; this additional risk is eliminated if a progestogen is given continuously. However, this should be weighed against the increased risk of breast cancer.

Risk of ovarian cancer
Long-term use of combined HRT or oestrogen-only HRT is associated with a small increased risk of ovarian cancer. This excess risk disappears within a few years of stopping.

Risk of venous thromboembolism
Women using combined or oestrogen-only HRT are at an increased risk of deep vein thrombosis and of pulmonary embolism especially in the first year of use.

In women who have predisposing factors (such as a personal or family history of deep vein thrombosis or pulmonary embolism, severe varicose veins, obesity, trauma, or prolonged bed-rest) it is prudent to review the need for HRT, as in some cases the risks of HRT may exceed the benefits.

Travel involving prolonged immobility further increases the risk of deep vein thrombosis.

Although the level of risk of thromboembolism associated with non-oral routes of administration of HRT has not been established, it may be lower for the transdermal route compared to the oral route; studies have found the risk associated with transdermal HRT to be no greater than the baseline population risk of thromboembolism.

Risk of stroke
Risk of stroke increases with age, therefore older women have a greater absolute risk of stroke. Combined HRT or oestrogen-only HRT increases the risk of stroke.

Risk of coronary heart disease
HRT does not prevent coronary heart disease and should not be prescribed for this purpose. There is an increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause. Although very little information is available on the risk of coronary heart disease in younger women who start HRT close to the menopause, studies suggest a lower relative risk compared with older women.

Risk of breast cancer
With systemic use:
HRT use is associated with an increased risk of breast cancer—see Important safety information.

Radiological detection of breast cancer can be made more difficult as mammographic density can increase with HRT use.

Question 24

Which situations would require gradual dose reduction with steroid use?

Answer 24

• recieved more than 40mg prednisolone (or equivalent) daily for more than one week
• been given repeat doses in the evening
• recently repeated courses ( particulalrly for more than 3 weeks)
• Taken a short course within 1 year of stopping long term therapy

Question 25

how can prednisolone use affect infections such as chicken pox and shingles

Answer 25

Infections

Prolonged courses of corticosteroids increase susceptibility to infections and severity of infections; clinical presentation of infections may also be atypical. Serious infections e.g. septicaemia and tuberculosis may reach an advanced stage before being recognised, and amoebiasis or strongyloidiasis may be activated or exacerbated (exclude before initiating a corticosteroid in those at risk or with suggestive symptoms). Fungal or viral ocular infections may also be exacerbated.

Chickenpox

Unless they have had chickenpox, patients receiving oral or parenteral corticosteroids for purposes other than replacement should be regarded as being at risk of severe chickenpox. Manifestations of fulminant illness include pneumonia, hepatitis and disseminated intravascular coagulation; rash is not necessarily a prominent feature. Passive immunisation with varicella–zoster immunoglobulin is needed for exposed non–immune patients receiving systemic corticosteroids or for those who have used them within the previous 3 months. Confirmed chickenpox warrants specialist care and urgent treatment. Corticosteroids should not be stopped and dosage may need to be increased.

Measles

Patients taking corticosteroids should be advised to take particular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. Prophylaxis with intramuscular normal immunoglobulin may be needed.

Question 26

What are the signs of jaundice?

Answer 26

Skin and eyes: Yellowing of the skin and the whites of the eyes, which can look brown in severe cases
Urine: Dark or brown-colored urine
Stools: Pale or clay-colored stools that are difficult to flush away
Itching: Itchy skin, also known as pruritis
Abdomen: Pain or discomfort in the upper right side of the abdomen, where the liver is located

Question 27

which corticosteroid is indicated for neuropathic postural hypotension

Answer 27

Fludrocortisone